Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-xL
Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-xL
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DOI：
10.1073/pnas.96.26.14871
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
Huang, DCS;Hahne, M;Strasser, A
Fas激活可触发多种细胞类型的凋亡。抗Fas抗体的研究对Fas信号传导产生了相互矛盾的结果，特别是Bcl-2家族在这一过程中的作用。生理配体和抗Fas抗体的比较表明，只有广泛的Fas聚集（通过膜结合Fast或聚集的可溶性Fast）才能持续触发细胞凋亡，而抗体可以作为死亡激动剂或拮抗剂。对转基因小鼠细胞系和原代细胞Fas信号的研究表明，FADD/MORT1和caspase-8是细胞凋亡所必需的。相比之下，Bcl-2或Bcl-x(L)不能阻断快速诱导的淋巴细胞或肝细胞凋亡，这表明Fas诱导细胞死亡的信号通路与Bcl-2家族调控的凋亡途径是不同的。
Fas activation triggers apoptosis in many cell types. Studies with anti-fas antibodies have produced conflicting results on Fas signaling, particularly the role of the Bcl-2 family in this process. Comparison between physiological ligand and anti-Fas antibodies revealed that only extensive Fas aggregation, by membrane bound Fast or aggregated soluble Fast consistently triggered apoptosis, whereas antibodies could act as death agonists or antagonists. Studies on Fas signaling in cell lines and primary cells from transgenic mice revealed that FADD/MORT1 and caspase-8 were required for apoptosis. In contrast, Bcl-2 or Bcl-x(L) did not block Fast-induced apoptosis in lymphocytes or hepatocytes, demonstrating that signaling for cell death induced by Fas and the pathways to apoptosis regulated by the Bcl-2 family are distinct.